Categorization of Clinical Trials

Clinical trials are often categorized into four phases, with a given trial being identified as belonging to one of them. Traditional descriptions are as follows  

A more informative alternative system of categorization was provided by the 

ICH their nomenclature, presented in Table 4.1, is much more descriptive of the 

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While this system of categorizing preapproval clinical trials is widespread, unfortunately it is not used consistently. As Turner (2007) noted, two studies with the same aims may be classified into different phases, and two studies classified into the same phase may have different aims. An alternative system has been suggested by the ICH. 

Only two randomized, controlled trials have been completed, and neither provides anything like compelling data (Table 2.6). Chouinard and Albright (1997) conducted a unique evaluation of a subset of patients from a previously conducted clinical trial. Subjects were categorized and profiled at baseline and end point according to clinical severity, and a group of psychiatric nurses were asked to rate various aspects of likely outcome and quality of life to each profile (mild, moderate or severe symptoms). Health state utilities were then calculated risperidone was found to provide more than double the number of quality-adjusted life years compared with haloperidol. Csernansky and Okamoto (1999) conducted a rather more conventional trial, but included no economic analyses. However, they did find that the use of risperidone substantially reduced relapse rates compared with haloperidol—an outcome likely to have a positive impact on cost-effectiveness. 

Much like the previous demographics table example, the majority of the tables generated for clinical trial reporting compare a set of continuous and/or categorical variables across treatment groups. The purpose is to see whether therapy groups are comparable or whether they differ in some way. These kinds of tables include the following ... 

A further issue is that we very rarely see strictly categorical outcomes in practice in our clinical trials it is much more common to have an ordering of the categories. 

Before discussing how clinical data are described and analyzed, it is helpful to introduce several categories of data. Data are numerical representations of information, and different forms of numerical information have different characteristics that permit (or do not permit) certain analyses to be conducted on them. In clinical research, the term variable is often used when describing data for a particular characteristic of interest, since values for participants in a clinical trial will vary from one individual to another. Clinical data can fall within several categories, including numerical (continuous and discrete) data and categorical (ordinal and nominal) data. 

Pharmaceutical clinical trials are often categorized into various phases, with any given trial being identified as belonging to one of them. These categories include Phase I, Phase II, and Phase III, and this common nomenclature was employed in Chapter 1 since it is likely that you were already familiar with it. However, there are alternate systems of categorization that are arguably more informative. A traditional description of phases is as follows ... 

However, in 531 eligible patients enrolled in a US Public Health Service Cooperative Trial of Short-Course Chemotherapy of Pulmonary Tuberculosis, of whom 58% were classified as alcoholic, although the alcoholics had more abnormal concentrations of aspartate transaminase before and during therapy, there was no significant difference between the alcoholics and non-alcoholics in the incidence of adverse reactions, including hepatotoxic reactions (92). The authors concluded that in the absence of clinically significant and persistent pretreatment abnormalities of hepatic function tests, rifampicin and isoniazid are not contraindicated in patients categorized as alcoholic. 

Medical Affairs departments are frequently capable of conducting various types of clinical research. The type of research culminating in the further categorization of the efficacy and safety of a new medicine can take the route of conventional phase III clinical development, sometimes conducted by a Medical Affairs division, whereby a new indication is sought. Another approach is to perform necessary clinical trials and seek approval to promote features of benefit-risk that are supported by clinical data, with or without requesting change of registered label use. This phase of... 

A common system of categorization for preap-proval clinical trials includes Phase 1, Phase 11, and Phase 111 clinical trials (Phase IV clinical trials are conducted postapproval to collect additional information about a marketed drug). Phase 1, 11, and 111 clinical trials can be summarized as follows ... 

The ICH has published a series of Guidances on many aspects of conducting clinical trials (see www.ich.org). One of these, ICH Guidance E8 (1997), provides an alternative approach to categorizing clinical trials, classifying them according to their objective. This system is shown in Table 2.1. 

Chapter 10 Confirmatory clinical trials Analysis of categorical efficacy data... 

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